Strategy of paramyxovirusto attenuate cytopathicity

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Paramyxoviruses including simian virus 5(SV5)mediate membrane fusion through an interaction between viral envelope glycoproteins HN and F, in which the HN protein promotes fusion-inducing function of the F protein. I report here that the stalk region of SV5 HN protein is involved in the interaction with the F protein the same as those of other paramyxoviruses. Furthermore, I report for the first time that four discrete domains of the F proteins participate in the interaction with the FIN protein. As published previously, on the other hand, the T1 strain of SV5 displays reduced ability to induce cell-cell fusion and thus brings minimal cytopathicity to the virus-infected cells as compared to the prototype WR strain. To investigate the molecular mechanism of the attenuated cytopathicity of T1 virus, highly fusogenic variant was obtained from T1 virus by plaque cloning. This variant possessed three mutations L182R, K45 IT, and V536M in the FIN protein, with no mutation in the F protein. Notably, L182R mutation proved to raise the fusion-promoting function of the HN protein and that mutation of leucine at position 182 to other amino acids other than Ala also facilitates the fusion-promoting function of the HN protein. However, either of the recombinant WR viruses whose HN and/or F proteins had been replaced with the Ti counterparts were fusogenic, indicating that other T1 virus proteins such as M protein might contribute to the fusion-inhibiting function of the T1 FIN protein. Since T1 virus could perform multiple-step replication, the fusion between envelope and cell membrane seems to take place normally. We thus hypothesize that T1 FIN protein may suppresses cell-cell fusion by transducing a signal to the intracellular molecules such as actin or vinculin that the L182R mutation or combination with WR M protein may somehow cancel this suppression of signal transduction.